title: T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice.
abstract: BACKGROUND
  Immunization against amyloid-β (Aβ), the peptide that accumulates in the form of senile plaques and in the cerebrovasculature in Alzheimer's disease (AD), causes a dramatic immune response that prevents plaque formation and clears accumulated Aβ in transgenic mice. In a clinical trial of Aβ immunization, some patients developed meningoencephalitis and hemorrhages. Neuropathological investigations of patients who died after the trial showed clearance of amyloid pathology, but also a powerful immune response involving activated T cells probably underlying the negative effects of the immunization.
  
  
  RESULTS
  To define the impact of T cells on this inflammatory response we used passive immunization and adoptive transfer to separate the effect of IgG and T cell mediated effects on microhemorrhage in APPPS1 transgenic mice. Neither anti Aβ IgG nor adoptively transferred T cells, alone, led to increased cerebrovascular damage. However, the combination of adoptively transferred T cells and passive immunization led to massive cerebrovascular bleeding that ranged from multiple microhemorrhages in the parenchyma to large hematomas.
  
  
  CONCLUSIONS
  Our results indicate that vaccination can lead to Aβ and T cell induced cerebral micro-hemorrhages and acute hematomas, which are greatly exacerbated by T cell mediated activity.
authors.affiliation: MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Alzheimer's Disease Research Laboratory, 02129 Charlestown, MA USA. bhyman@partners.org.
authors.forename: Melanie
authors.initials: M
authors.lastname: Meyer-Luehmann
authors.forename: J Rodrigo
authors.initials: JR
authors.lastname: Mora
authors.forename: Matthew
authors.initials: M
authors.lastname: Mielke
authors.forename: Tara L
authors.initials: TL
authors.lastname: Spires-Jones
authors.forename: Alix
authors.initials: A
authors.lastname: de Calignon
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman